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Severe nail toxicity induced by FGFR inhibitor in FGFR2-rearranged cholangiocarcinoma
Chiaki Kondo1, Ayako Mitsuma1, Yuichi Ando1
1Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Tsurumai-Cho, Showa-Ku, NagoyaNagoya, 466-8550 Japan.
Abstract:
FGFR2 gene fusions are identified in approximately 10-16% of patients with intrahepatic cholangiocarcinoma and are targets of FGFR tyrosine kinase inhibitors (TKIs). While these agents are clinically effective, nail disorders are a documented class-effect toxicity, occurring in approximately 40%-50% of patients treated with various FGFR inhibitors, often impairing quality of life. We report a case of a 53-year-old man with locally advanced intrahepatic cholangiocarcinoma refractory to standard chemotherapy (cisplatin/gemcitabine, S-1) and proton beam therapy. Comprehensive genomic profiling revealed FGFR2::WAC and KCNH8::FGFR2 fusion genes. Treatment was initiated with pemigatinib (13.5 mg/day). One month later, painful nail deformities appeared, followed by thickening, black discoloration, and brittleness. Despite a dose reduction to 9 mg/day, the nail toxicity remained. Consequently, high-potency topical corticosteroids were administered, and symptoms subsided. After disease progression, the treatment was switched to futibatinib (16 mg daily), and during the three-month administration, the nail disorders did not worsen and tended to improve. In conclusion, we describe a case where severe nail toxicity induced by a reversible FGFR inhibitor was managed by switching to futibatinib and utilizing topical corticosteroids. Although effective treatments for nail-related events are limited, this case suggests the effectiveness of steroid ointments.
Insights
FGFR2 gene fusions drive intrahepatic cholangiocarcinoma. FGFR tyrosine kinase inhibitors (TKIs) can cause severe nail toxicity, but topical corticosteroids and switching to futibatinib may effectively manage these side effects.
Area of Science:
- Oncology
- Pharmacology
Background:
- FGFR2 gene fusions are present in 10-16% of intrahepatic cholangiocarcinoma (ICC) cases.
- FGFR tyrosine kinase inhibitors (TKIs) target these fusions but commonly cause nail toxicity (40-50% incidence).
- Nail disorders associated with FGFR inhibitors significantly impact patient quality of life.
Purpose of the Study:
- To report a case of severe nail toxicity in a patient with ICC treated with FGFR inhibitors.
- To describe the management of this toxicity using topical corticosteroids and a switch in FGFR inhibitor therapy.
- To highlight potential treatment strategies for FGFR inhibitor-induced nail disorders.
Main Methods:
- A patient with locally advanced ICC refractory to standard treatments received pemigatinib.
- Comprehensive genomic profiling identified FGFR2 fusions.
- Nail toxicity was managed with dose reduction, topical corticosteroids, and subsequent treatment with futibatinib.
Main Results:
- The patient developed severe, painful nail deformities (thickening, discoloration, brittleness) on pemigatinib.
- Dose reduction of pemigatinib did not resolve the toxicity.
- Topical corticosteroids led to symptom improvement.
- Switching to futibatinib halted progression and improved nail disorders.
Conclusions:
- Severe nail toxicity from FGFR inhibitors can be managed effectively.
- Topical corticosteroids show promise in alleviating symptoms.
- Switching to a different FGFR inhibitor, such as futibatinib, may be a viable strategy for patients experiencing significant side effects.
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